Responsive　nano-drug　delivery　systems,　especially　multi-responsive　systems,　based　on　the　complex　characteristics　of　the　tumor　microenvironment　(TME),　such　as　acidic　pH,　hypoxia,　and　hydrogen　peroxide　(H2O2)　overexpression,　could　enhance　the　biological　activity　of　the　drugs　and　reduce　the　side　effects.　In　this　study,　a　H2O2/glutathione　(GSH)　procedurally　activatable　nanoplatform　(Cu9S5-PEG/DOX　NSs)　was　prepared　as　a　vector　of　drugs　released　by　responsive　morphologic　transformation　and　the　co-activated　Fenton　agent　for　tumor-specific　synergistic　therapy.　After　endocytosis　into　tumor　cells,　Cu9S5-PEG/DOX　NSs　were　initially　oxidized　by　over-expressed　H2O2　and　transformed　from　nanosheets　to　nanoflowers,　leading　to　the　release　of　doxorubicin　(DOX).　Subsequently,　Cu9S5　nanoflowers　(Cu9S5　NFs)　reacted　with　the　local　GSH,　liberated　a　large　number　of　copper　ions,　and　induced　GSH　depletion.　The　released　DOX　promoted　the　generation　of　intracellular　H2O2　through　cascade　reactions,　which　were　further　utilized　to　facilitate　the　release　of　DOX　and　generate　toxic　hydroxyl　radicals　(OH)　via　a　copper-based　Fenton-like　reaction.　Cu9S5-PEG/DOX　NSs　sequentially　activated　by　H2O2　and　GSH　in　tumor　cells　exhibited　relatively　high　cytotoxicity,　whereas　normal　cells　were　still　alive.　This　nanoplatform,　as　a　procedurally　activatable　delivery　system,　may　have　excellent　potential　for　tumor-specific　synergistic　therapy.